Although calmodulin is found in all eukaryotic cells and serves many functions in its interaction with enzymes, peptides and drugs, its calcium-induced conformational changes are still not well understood. It is proposed that the powerful techniques of FTIR and FTNMR spectroscopy be exploited to try to answer some of the questions currently being asked about this system: What effects do temperature and pH changes have on metal-ion binding sites in calmodulin and how are these effects influenced by ion size and charge? Do different metal ions compete for the same binding sites or do they occupy different sub-sites in the binding region? Why do some ions appear to increase alpha helicity whereas others seem to decrease it? Spectral subtraction and self-doconvolution methods will be used to analyze the FTIR data. It is proposed that high field Al-27, Mg- 25, Mn-55 and Zn-67 FTNMR be used to monitor directly the metal-ion binding in calmodulin. Long-range goals include investigation of other calcium-binding proteins to establish whether binding behavior is regio-/site-specific or protein- specific for this class of proteins.